Thursday, January 17, 2013
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Chimeric antigen receptors (CARs) that require dual-antigen
binding for activation
cells engineered to express a CAR and a chimeric co-stimulatory receptor
could enhance the tumor specificity of targeted T cell therapies. T cells
expressing CARs can trigger a tumor antigen-specific immune response but also
can cause toxicity if the targeted antigen is not exclusively expressed by
tumor cells. To increase specificity, T cells were engineered to carry a CAR
that induces T cell activation only when a second co-stimulatory receptor
engages with another tumor-specific antigen. In a mouse model of prostate
cancer, T cells engineered to bind both prostate
stem cell antigen (PSCA) and prostate-specific
membrane antigen (PSMA; FOLH1;
decreased the growth of PSCA+/PSMA+ tumors but not the growth of tumors expressing only
one of the two antigens. Next steps include developing additional strategies
to increase the safety of the T cell therapy.
Published online Jan. 17, 2013
Patent application filed;
available for licensing
Kloss, C.C. et al. Nat.
Biotechnol.; published online Dec. 16, 2012;
Contact: Michel Sadelain, Memorial Sloan-Kettering Cancer
Center, New York, N.Y.
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